2,2,5,7-tetramethyl-1,2,3,4-tetrahydro-1,8-naphthyridine | 861205-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,2,5,7-tetramethyl-1,2,3,4-tetrahydro-1,8-naphthyridine
• 英文别名: Onabmysobpbkiu-uhfffaoysa-；2,2,5,7-tetramethyl-3,4-dihydro-1H-1,8-naphthyridine
• CAS: 861205-48-3
• 化学式: C₁₂H₁₈N₂
• 分子量: 190.288
• InChiKey: ONABMYSOBPBKIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2,5,7-tetramethyl-1,2,3,4-tetrahydro-1,8-naphthyridine 在 1,3-二溴-5,5-二甲基海因 作用下， 以 二氯甲烷 为溶剂， 反应 0.67h， 以75%的产率得到6-bromo-2,2,5,7-tetramethyl-1,2,3,4-tetrahydro-1,8-naphthyridine
  参考文献：
  名称：

  Regioselective Addition ofn-Alkyllithiums to α,α′-Disubstituted-1,8-Naphthyridines: Synthesis of 6-Amino-3-Pyridinol Analogs of α-Tocopherol

  摘要：

  在非极性溶剂（如 Et2O-己烷混合物）中，将正烷基锂加入到δ,δ′-二取代的-1,8-萘啶中。在极性溶剂（如四氢呋喃）中，烷基锂充当碱而不是亲核体。对于能够与（烷基）锂试剂进行五元环螯合的底物，可实现区域选择性加成。以 TBS 保护醇作为共螯合基团的底物具有最佳的产率和区域选择性。这种方法被成功用于制备五甲基色醇（PMC）的两种 6-氨基-3-吡啶醇类似物，PMC 是一种δ-生育酚衍生物，其异戊烯侧链被截断为一个甲基。

  DOI：

  10.1055/s-2005-865308
• 作为产物：
  描述：

  2-氨基-4,6-二甲基吡啶 在 三乙烯二胺 、 palladium on activated charcoal 、 iron(II) sulfate 咪唑 、 4-二甲氨基吡啶 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 NO₂PhSO₃Na 、 硫酸 、 四丁基氟化铵 、 氢气 、 碘 、 硼酸 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 三苯基膦 、 potassium hexacyanoferrate(III) 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 12.17h， 生成 2,2,5,7-tetramethyl-1,2,3,4-tetrahydro-1,8-naphthyridine
  参考文献：
  名称：

  Regioselective Addition ofn-Alkyllithiums to α,α′-Disubstituted-1,8-Naphthyridines: Synthesis of 6-Amino-3-Pyridinol Analogs of α-Tocopherol

  摘要：

  在非极性溶剂（如 Et2O-己烷混合物）中，将正烷基锂加入到δ,δ′-二取代的-1,8-萘啶中。在极性溶剂（如四氢呋喃）中，烷基锂充当碱而不是亲核体。对于能够与（烷基）锂试剂进行五元环螯合的底物，可实现区域选择性加成。以 TBS 保护醇作为共螯合基团的底物具有最佳的产率和区域选择性。这种方法被成功用于制备五甲基色醇（PMC）的两种 6-氨基-3-吡啶醇类似物，PMC 是一种δ-生育酚衍生物，其异戊烯侧链被截断为一个甲基。

  DOI：

  10.1055/s-2005-865308

文献信息

• Tetrahydro-1,8-naphthyridinol Analogues of α-Tocopherol as Antioxidants in Lipid Membranes and Low-Density Lipoproteins
  作者：Tae-gyu Nam、Christopher L. Rector、Hye-young Kim、Andreas F.-P. Sonnen、Roland Meyer、Werner M. Nau、Jeffrey Atkinson、Julia Rintoul、Derek A. Pratt、Ned A. Porter

  DOI：10.1021/ja072371m

  日期：2007.8.1

  Recently we demonstrated that the C(7)-unsubstituted tetrahydro-1,8-naphthyridin-3-ol has more than an order of magnitude better peroxyl radical trapping activity than alpha-tocopherol (alpha-TOH) in inhibited autoxidations in benzene. In order to prepare analogues more structurally related to alpha-TOH for further studies in vitro and in vivo, we developed synthetic approaches to C(7)-monoalkyl and C(7)-dialkyl analogues using a sequence involving (1) AgNO3-mediated hydroxymethyl radical addition to 1,8-naphthyridine, (2) regioselective alkyllithium addition by cyclic chelation in a nonpolar solvent, (3) iodination of the naphthyridine at C(3), and (4) CuI-medidated benzyloxylation of the aryl iodide followed by catalytic hydrogenolysis. An alpha-TOH isostere was prepared by a Wittig coupling of a C-16 side chain identical to that of alpha-TOH to the naphthyridinols. The C(7)-mono- and dialkyl analogues exhibited more than an order of magnitude higher antioxidant activity (k(inh) = (5.3-6.1) x 10(7) M-1 s(-1)) than alpha-TOH (k(inh) = 0.35 x 10(7) M-1 s(-1)) in benzene, as determined by a newly developed peroxyl radical clock. In addition to the strong antioxidant activity in benzene, the closest alpha-TOH analogue (naphthyridinol-based tocopherol, N-TOH) showed excellent inhibition of the oxidation of cholesteryl esters in human low-density lipoprotein and spared endogenous alpha-TOH in these experiments. Lateral diffusion of N-TOH in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes was comparable to that of alpha-TOH, suggesting that it will have good antioxidant characteristics in both membranes and lipoproteins. Furthermore, a binding assay using a fluorescent tocopherol analogue showed that N-TOH binds to recombinant human tocopherol transfer protein better than alpha-TOH itself, suggesting that distribution of unnatural antioxidants such as N-TOH in vivo is possible.
• Regioselective Addition of<i>n</i>-Alkyllithiums to α,α′-Disubstituted-1,8-Naphthyridines: Synthesis of 6-Amino-3-Pyridinol Analogs of α-Tocopherol
  作者：Derek A. Pratt、Ned A. Porter、Tae-gyu Nam、Maikel Wijtmans

  DOI：10.1055/s-2005-865308

  日期：——

  n-Alkyllithiums were added to α,α′-disubstituted-1,8-naphthyridines in non-polar solvents such as Et2O-hexane mixtures. In polar solvents such as THF, alkyllithium acts as a base rather than a nucleophile. Regioselective addition was achieved for substrates capable of five-membered cyclic chelation of the (alkyl)lithium reagent. Substrates with a TBS-protected alcohol as the co-chelating moiety afforded the best combination of yield and regioselectivity. This methodology was successfully employed in the preparation of two 6-amino-3-pyridinol analogs of pentamethylchromanol (PMC), an α-tocopherol derivative with its isoprenoid side chain truncated to a methyl group.

  在非极性溶剂（如 Et2O-己烷混合物）中，将正烷基锂加入到δ,δ′-二取代的-1,8-萘啶中。在极性溶剂（如四氢呋喃）中，烷基锂充当碱而不是亲核体。对于能够与（烷基）锂试剂进行五元环螯合的底物，可实现区域选择性加成。以 TBS 保护醇作为共螯合基团的底物具有最佳的产率和区域选择性。这种方法被成功用于制备五甲基色醇（PMC）的两种 6-氨基-3-吡啶醇类似物，PMC 是一种δ-生育酚衍生物，其异戊烯侧链被截断为一个甲基。

表征谱图